iPSC-derived CD16/IL-15RF-expressing CD38-eliminated NK Cells FT538

{
  "id": "MLC-T-ONC-014563",
  "term": "iPSC-derived CD16/IL-15RF-expressing CD38-eliminated NK Cells FT538",
  "field": "Oncology and biomedicine",
  "definition": "An allogeneic, off-the-shelf, natural killer (NK) cell product derived from a clonal master induced pluripotent stem cell (iPSC) line, and engineered and CRISPR-edited to express a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor and a recombinant fusion of IL-15 and IL-15 receptor alpha (IL-15RF), and to eliminate CD38 expression, with potential immunostimulatory and antineoplastic activities. Upon administration, iPSC-derived CD16/IL-15RF-expressing CD38-eliminated NK cells FT538 bind to stress-induced ligands on tumor cells, leading to tumor cell lysis and release of tumor neoantigens. Additionally, FT538 NK cells secrete inflammatory cytokines and chemokines, thereby enhancing T-cell activity and recruitment to the tumor site. IL-15RF promotes the survival of NK cells and enhances the cytotoxic effect of the NK cells and the activated anti-tumor T cells. When used in combination with monoclonal antibodies, the hnCD16 Fc receptor of FT538 binds to the Fc portion of tumor cell-bound monoclonal antibodies, leading to NK cell activation, cytokine secretion and enhanced antibody-dependent cellular cytotoxicity (ADCC). CD16, also known as Fc-gamma receptor III, is normally expressed on the surface of NK cells, neutrophils, monocytes and macrophages, and plays a key role in initiating ADCC. It is often downregulated in certain cancers, thereby inhibiting the anti-tumor immune response. The lack of CD38 in FT538 NK cells prevents NK cell fratricide upon co-administration with a CD38-targeting monoclonal antibody as CD38 is normally expressed on the surface of activated NK cells. This enhances ADCC mediated by CD38-targeting monoclonal antibodies.",
  "synonyms": [
    "induced pluripotent stem cell-derived CD16/IL-15RF-expressing CD38-eliminated natural killer cells FT538"
  ],
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/ipsc-derived-cd16-il-15rf-expressing-cd38-eliminated-nk-cells-ft538/"
}